Alternative splicing is now commonly thought to affect more than half of all human genes. Recent studies have investigated not only the scope but also the biological impact of alternative splicing on a large scale, revealing that its role in generating proteome diversity may be augmented by a role in regulation. For instance, protein function can be regulated by the removal of interaction or localization domains by alternative splicing. Alternative splicing can also regulate gene expression by splicing transcripts into unproductive mRNAs targeted for degradation. To fully understand the scope of alternative splicing, we must also determine how many of the predicted splice variants represent functional forms. Comparisons of alternative splicing between human and mouse genes show that predominant splice variants are usually conserved, but rare variants are less commonly shared. Evolutionary conservation of splicing patterns suggests functional importance and provides insight into the evolutionary history of alternative splicing.